Persistant attractants for the mediterranean fruit fly, the method of preparation and method of use

ABSTRACT

Novel attractants for the Mediterrean Fruit Fly, &#34;Medfly,&#34; are disclosed. The attractants comprise isomeric blends of esters of iodo-trans-2-methylcyclohexanecarboxylic acid. In use, the attractants are competitive in attraction with the &#34;standard&#34; Medfly attractant, Trimedlure, &#34;TML,&#34; but are much more persistent than TML.

This application is a continuation-in-part of application Ser. No.07/042,920, filed Apr. 27, 1987, now U.S. Pat. No. 4,764,366.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to novel attractants for the Mediterranean FruitFly, Ceratitis capitata Wiedmann, hereinafter referred to as the"Medfly." More particularly, the present invention relates to novelisomeric blends of aliphatic esters ofiodo-trans-2-methylcyclohexanecarboxylic acid, the method of theirpreparation and the method of use thereof to attract the Medfly forprolonged periods of time.

2. Description of the Prior Art

Attacking over 250 varieties of fruits, nuts and vegetables, the Medflyis one of our most serious crop pests. Found predominately in Hawaii,Central America, and subtropical regions of the world, the Medfly hasperiodically invaded the mainland of the United States causing majoreconomic losses. Consequently, there exists a great need for effectiveprograms to control this pest.

Several attractants for the Medfly are known. Siglure (1-methylpropyltrans-6-methyl-3-cyclohexenecarboxylate) was the first synthetic lurefound to have significant attraction to the Medfly. Medlure(1-methylpropyl 4(and 5)-chloro-trans-2-methylcyclohexanecarboxylate)and trimedlure (1,1-dimethylethyl 4(and5)-chloro-trans-2-methylcyclohexanecarboxylate), hereinafter referred toas "TML," were later reported to be greatly superior as Medflyattractants.

Currently, TML is the "standard" attractant most widely used in trapsfor survey and detection of the Medfly. TML evaporates rapidly duringhot weather thereby necessitating frequent and costly rebaiting of thetraps. Further, the short residual life of TML (as well as Medlure andSiglure) mitigates against the development of an economicalmale-annihilation formulation of attractant plus insecticide. TML alsoforms crystals during cold-weather storage so that the amount of theattractant is reduced in the supernatant. Because these crystals do notreadily redissolve, special storage problems can occur in larger volumeprograms.

SUMMARY OF THE INVENTION

An object of this invention is to provide novel attractants which arehighly attractive to the Medfly for prolonged periods of time.

Another object of this invention is to provide persistent Medflyattractants which are comparable in attraction with TML but do notpossess the deficiencies associated with TML.

We have accomplished the aforementioned objects by providing certainisomeric blends of lower alkyl esters of 4(and5)-iodo-trans-2-methylcyclohexanecarboxylic acid which when applied inan amount sufficient to attract the Medfly are highly effective forprolonged periods of time. In addition to being much more persistentthan TML, the esters of the invention are not prone to crystallizationas is TML, and may be more facilely and economically produced than TML.

DETAILED DESCRIPTION OF THE INVENTION

In general, esters useful in the present invention are represented bythe general formulae ##STR1## wherein --CH₃ and --COOR are in thetrans-configuration and I is in both the equatorial and axialconformation; and wherein R is an aliphatic radical having from 1-5carbon atoms and is selected from the group consisting of lower alkylsand fluoro-substituted lower alkyls, said R in each of formulae I and IIbeing identical.

For purposes of the invention, the term "4 and 5" is used herein todesignate a mixture of the 4- and 5-iodo isomers wherein the iodo atomsof the invention esters are in both an equatorial and axialconformation, thus providing a blend of four stereoisomers for eachester. The four stereoisomers are herein designated A₁, A₂, B₁ and B₂ asfollows: ##STR2##

Examples of esters useful in the present invention are methyl 4(and5)-iodo-trans-2-methylcyclohexanecarboxylate; ethyl 4(and5)-iodo-trans-2-methylcyclohexanecarboxylate; propyl 4(and5)-iodo-trans-2-methylcyclohexanecarboxylate; 1-methylpropyl 4(and5)-iodo-trans-2-methylcyclohexanecarboxylate; 2,2,2-trifluoroethyl 4(and5)-iodo-trans-2-methylcyclohexanecarboxylate;1-methyl-2,2,2-trifluoroethyl 4(and5)-iodo-trans-2-methylcyclohexanecarboxylate;2,2,3,3,3-pentafluoro-1-methylpropyl 4(and5)-iodo-trans-2-methylcyclohexanecarboxylate; and2,2,3,3,4,4,4-heptafluoro-1-methylbutyl 4(and5)-iodo-trans-2-methylcyclohexanecarboxylate.

Esters useful in the present invention maybe prepared as follows: Thecorresponding trans-6-methyl-3-cyclohexenecarboxylic acid (as preparedby a Diels-Alder reaction) is heated in a pressure vessel for 3 to 6hours at elevated temperatures with aqueous hydriodic acid in thepresence of an organic solvent, such as dioxane. The resultantiodo-trans-2-methylcyclohexanecarboxylic acid is a mixture of the 4- and5-iodo isomers and is converted to the corresponding acid halide byreacting with a suitable halogenating agent, such as thionyl chloride,phosphorus trichloride or phosphorus tribromide, under mild conditions,preferably at room temperature. The acid halide is then reacted with theappropriate alcohol in a suitable solvent such as benzene or anhydrousethyl ether in the presence of a hydrochloric acid scavenger, such aspyridine, to yield the ester.

Isolation of the ester is accomplished by sequentially washing the crudereaction mixture with dilute acid, dilute base and saturated saltsolutions. The crude product is thereafter dried over a suitable dryingagent, filtered and the solvent removed. Final purification isaccomplished by fractional distillation under high vacuum. Individualstereoisomers of the esters can be separated by high-performance liquidchromotography.

The stereoisomeric content of the esters can be easily varied bychanging the reaction temperature during preparation of the ester. Forexample, invention esters synthesized by the addition of hydrogen iodideto the Diels-Alder acid adduct at moderately elevated temperatures, i.e.from about 65° C. to 80° C., consist of a isomeric blend which hasisomers A₁ and A₂ as its major components, with isomers B₁ and B₂comprising about 10% to 20% of the blend. Esters synthesized by theaddition of hydrogen iodide to the Diels-Alder acid adduct to about 95°C. to 130° C. consist of an isomeric blend which consists of greaterthan 50% of isomers B₁ and B₂. Consequently, the higher the temperaturethe greater the B₁ /B₂ isomeric content in the resulting ester.

Of the four stereoisomers, the most attractive isomer is isomer B₁having an equatorial iodo atom attached at the 5 carbon atom. Forcommercial practicalness, it is preferred to use a blend of isomersconsisting predominantly of isomers B₁ and B₂. Preferably, the blendcomprises an isomeric content of from about 50% to 100% of isomers B₁and B₂ with isomers A₁ and A₂ comprising from about 0% to 50% of theblend.

The esters may be used as is or they may be dissolved in volatile inertsolvents such as liquid hydrocarbons, emulsified in water, or admixedwith any other solid or inert liquid carrier. When used in actualpractice in the field, the compounds may be impregnated on a solidcarrier such as paper, cloth, sawdust, wood chips, or other absorbentmaterial. The attractants may also be dispersed into the atmosphere byspraying or by dipping wicks into containers holding the estercomposition. Further, the attractants may be used in bait traps usuallyprovided with means to prevent the exit of insects so that the size andlocation of infestations may be ascertained.

For optimum results, the esters of the invention should be used in asubstantially pure form, that is, the ester must be free of undesirablecontaminants that tend to mask or otherwise inhibit their effectivenessas an attractant. It is within the compass of the invention to use theesters either individually or in combination. The invention esters mayalso be used with other Medfly attractants of control agents, such asinsecticides, chemosterilants or the like. When used, however, theseagents should be used in an amount which, as readily determined by oneskilled in the arts, will not interfere with the effectiveness of theinvention esters.

Although the preparative procedures described above are the preferredsynthesis for the compounds of the invention, it is within the scope ofthis invention to prepare the esters using any suitable hydriodic acidaddition and esterification procedures.

The invention is further demonstrated by the following examples whichare intended only to further illustrate the invention and not to limitthe scope of the invention as defined by the claims.

EXAMPLE 1

The preparation of a blend of ethyl 4(and 5)-iodo-trans-2-methylcyclohexanecarboxylate comprising more than 50% of isomers B₁ and B₂using the Diels-Alder acid adduct intermediate is hereinafterillustrated.

21 g of trans-6-methyl-3-cyclohexenecarboxylate acid (0.15 mole) wereadded to a pressure bottle along with 60 ml of 57% hydriodic acid and 30ml of p-dioxane. The pressure bottle was equipped with a magneticstirrer, securely capped, and placed in an oil bath held at 115° to 125°C. The reaction mixture was stirred vigorously while being held in thebath for 3 hours. After cooling, the reaction mixture was poured intowater and the organic layer was taken up in either. The ether layer waswashed 2 times with water, then the organic acid was extracted from thecrude reaction mixture with 10% aqueous sodium hydroxide. The alkalineportion was strongly acidified. The released organic acid was taken upin ether and was washed 3 times with water, then with dilute sodiumbisulfite solution, again with water, dried over anhydrous magnesiumsulfate and filtered. After removal of the solvent the crude iodo acid(ca 36 g) was used directly in the acid chloride synthesis. 26.8 g ofthe iodo acid (0.1 mole) was dissolved in 25 ml of benzene and 9 ml ofthionyl chloride (0.125 mole) was added dropwise at room temperature.The reaction mixture was stirred overnight and the excess thionylchloride and benzene were removed under vacuum with slight warming (40°C.). The crude acid chloride was added dropwise to an excess of ethanol(12 ml) and 8 ml of pyridine in anhydrous ether. After standingovernight, the reaction mixture was extracted sequentially with water,dilute aqueous hydrochloric acid and sodium hydroxide and finally withsaturated salt solution. After drying over anhydrous magnesium sulfate,the crude product was isolated and purified by fractional distillationunder high vacuum, b.p. 81° C./0.15 mm Hg, n_(D) ²⁵ 1.5130, recoveredyield 15.0 g, approximately 67% of which consisted of isomers B₁ and B₂and 33% of isomers A₁ and A₂ (from gc peak height measurement). If theproduct darkens excessively after distillation, the excessive color canbe removed by washing the product with dilute sodium bisulfite solution.

EXAMPLE 2

An isomeric blend of propyl 4(and5)-iodo-trans-2-methylcyclohexanecarboxylate was synthesized in a 0.02mole reaction in accordance with the procedure described in Example 1,and purified by distillation under high vacuum, b.p. 85° C./0.15 mm,n_(D) ²⁵ 1.5065, recovered yield 2.67 g (about 67% isomers B₁ and B₂ andabout 33% isomers A₁ and A₂ (from gc peak height measurement).

EXAMPLE 3

To determine the effectiveness of the blends of the invention a fieldtest was conducted in a macadamia nut orchard at Keaau, Hawaii, inOctober 1987.

Medfly captures using isomeric blends of methyl, propyl, 1-methylethyl,1-methyl-2,2,2-trifluoroethyl and 2,2,2-trifluoroethyl 4(and5)-iodo-trans-2-methylcyclohexanecarboxylate were compared with thosecaptures obtained by using TML. The ester blends used were (1) blendswhich consisted of about 100% B₁ and B₂ isomers; and/or (2) normalblends, that is, blends comprising isomers A₁, A₂, B₁ and B₂ whereinisomers A₁ and A₂ comprise more than 50% of the blend.

Treatments were applied to cotton wicks (9.5 mm diam.×12.7 mm length;Johnson and Johnson No. 2) in standard Jackson sticky traps. Eachattractant was applied in a 0.025 ml dosage undiluted to a wick. Sixreplicates were used. The TML wick was allowed to age along with theother attractants. Sterile laboratory-reared medflies were releasedthroughout the test plot in a uniform manner at 0, 1, 2, 3, 4, 8, 10 and13 days posttreatment. Fresh sticky inserts were placed in the trapsprior to each release and remained in the trap throughout the testinterval.

The TML used in the tests was obtained commercially from UOP in EastRutherford, N.J.

Data was analyzed by analysis of variance, and means were separated byDuncan's multiple range test at the P=0.05 level (Duncan 1951). Theresults are recorded in Table I.

Table I clearly shows the high attraction and superior persistence ofester blends comprising only isomers B₁ and B₂ over the normal blends.All of the B₁ B₂ blends were significantly more attractive than theircorresponding normal blends. In no case throughout the test did thecatch of the normal mixture equal the catch obtained with thecorresponding B₁ B₂ blend. Of the ester blends tested, the B₁ B₂isomeric blend of the ethyl ester was the most attractive. Although notas initially attractive as the ethyl ester blend, the B₁ B₂ isomericblends of the propyl and the 1-methylethyl esters showed significantpersistence over TML. After 2 days TML began to fail while the propyland 1-methylethyl esters were effective up to 13 and 8 days,respectively. Further, the propyl and 1-methylethyl blends outlasted theethyl ester up to 5 and 2 days, respectively.

EXAMPLE 4

The relative attractiveness of the four stereoisomers of ethyl 4(and5-iodo-trans-2-methylcyclohexanecarboxylate, and mixtures thereof, weredetermined in a field test conducted in a macadamia nut orchard atKeaau, Hawaii, in February 1988.

Medfly captures obtained with fresh and aged TML was compared tocaptures obtained using the ethyl ester having the following isomericcontent: (1) high A₁ and A₂, that is, more than 50% of isomers A₁ and A₂; (2) isomer A₂ ; (3) isomers B₁ and B₂ ; (4) isomer B₁ and (5) isomerB₂ with ca. 2.5% of isomer B₁.

The bioassay was the same as described in Example 4 except that afreshly baited TML wick was added to the test prior to each fly releaseand medflies were released at 0, 1, 3, 4, 8, 9, 10, 11 and 14 dayspostreatment.

Data were analyzed in accordance with Example 4. The results arereported in Table II.

Table II shows that of the four stereoisomers of the ethyl ester, themost attractive isomer was the B₁ isomer. Traps with the B₁ isomer hadhigher mean catches than those of resh TML in the first 6 test periodsand in 7 of the 9 test periods overall. Medfly captures with blendscomprising the B₁ isomer were significantly as attractive as fresh TMLup to 10 days. All isomeric mixtures of the ethyl ester tested were morepersistent than aged TML which began to fail between days 1 and 3.

It is understood that modifications and variations may be made to theforegoing disclosure without departing from the spirit and scope of theinvention.

                                      TABLE I                                     __________________________________________________________________________    Attraction of the Mediterranean Fruit Fly to Esters of 4(and                  5)-Iodo-trans-2-methyl-                                                       cyclohexane-1-carboxylic Acid When Compared With Trimedlure (TML),            October,                                                                      1987, Keaau, Hawaii                                                                           Weighted mean catch/trap after indicated                                Isomer                                                                             days of exposure in the field.sup.b c                          Ester     blend.sup.a                                                                        0  1   2   3   4   8  10 13                                    __________________________________________________________________________    TML-aged       162a                                                                             176a                                                                              122bc                                                                             14f 0f  0e 0d 0c                                    Methyl    Normal                                                                             5f 5e  6f  9f  7ef 0e 0d 0c                                              B.sub.1 B.sub.2                                                                    31de                                                                             38d 45de                                                                              49de                                                                              48d 0e 0d 0c                                    Ethyl     B.sub.1 B.sub.2                                                                    157a                                                                             216a                                                                              190ab                                                                             200a                                                                              229a                                                                              93b                                                                              0d 0c                                    Propyl    Normal                                                                             33de                                                                             62cd                                                                              56de                                                                              97bc                                                                              91cd                                                                              52c                                                                              23b                                                                              6b                                              B.sub.1 B.sub.2                                                                    69bc                                                                             143ab                                                                             122bc                                                                             147ab                                                                             165ab                                                                             146a                                                                             65a                                                                              49a                                   1-Methylethyl                                                                           Normal                                                                             12ef                                                                             36d 49de                                                                              58cde                                                                             90cd                                                                              19d                                                                              7c 0c                                              B.sub.1 B.sub.2                                                                    47cd                                                                             84c 94cd                                                                              93bc                                                                              125bc                                                                             34cd                                                                             8c 0c                                    1-Methyl-2,2,2-                                                               trifluoroethyl                                                                          Normal                                                                             16ef                                                                             39d 33e 29ef                                                                              14e 0e 0d 0c                                              B.sub.1 B.sub.2                                                                    49cd                                                                             102bc                                                                             52de                                                                              64cd                                                                              65d 0e 0d 0c                                    2,2,2-Trifluoroethyl                                                                    Normal                                                                             107b                                                                             197a                                                                              207a                                                                              167a                                                                              144bc                                                                             0e 0d 0c                                    __________________________________________________________________________     .sup.a Normal blend is composed of 4 isomers, A.sub.1, A.sub.2, B.sub.1,      and B.sub.2 wherein isomers A.sub.1 and A.sub.2 are more than 50% of the      blend                                                                         .sup.b 6 replicates; 0.025 ml dosage?                                         .sup.c Catches followed by the same letter within a column are not            significantly different (P > 0.05; Duncan's [1951] multiple range test). 

                                      TABLE II                                    __________________________________________________________________________    Attraction Of The Mediterranean Fruit Fly To Varying Isomeric Blends of       Ethyl 4(and 5)-iodo-trans-2-methylcyclohexanecarboxylate And To Its           Individual                                                                    Isomers A.sub.2, B.sub.1, AND B.sub.2 When Compared With Trimedlure           (TML).                                                                        Isomer Weighted mean catch/trap after indicated days in the field.sup.b       Content.sup.a                                                                        0   1  3  4  8  9   10 11 14                                           __________________________________________________________________________    TML-(fresh)                                                                          152a                                                                              44ab                                                                             63a                                                                              92a                                                                              136a                                                                             130ab                                                                             125a                                                                             52b                                                                              119a                                         TML-(aged)                                                                           78bc                                                                              19b                                                                              10b                                                                              0c 0c 0d  0e 0d 0c                                           High A.sub.1 A.sub.2.sup.c                                                           19de                                                                              2c 5b 23b                                                                              15b                                                                              15c 12d                                                                              2cd                                                                              3b                                           A.sub.2                                                                              4e  0c 0c 0c 0c 0d  0e 0d 0c                                           High B.sub.1 B.sub.2.sup.c                                                           113ab                                                                             40ab                                                                             50a                                                                              109a                                                                             96a                                                                              91b 41bc                                                                             7c 0c                                           B.sub.1 B.sub.2                                                                      135ab                                                                             60a                                                                              65a                                                                              123a                                                                             126a                                                                             109ab                                                                             28cd                                                                             6c 0c                                           B.sub.1                                                                              172a                                                                              63a                                                                              73a                                                                              121a                                                                             139a                                                                             144a                                                                              103a                                                                             85a                                                                              116a                                         B.sub.2.sup.d                                                                        40cd                                                                              3c 8b 22b                                                                              15b                                                                              12c 1e 0d 0c                                           __________________________________________________________________________     .sup.a The 4 isomers that compose the trans blend are designated A.sub.1,     A.sub. 2, B.sub.1 and B.sub.2.                                                .sup.b Catches followed by the same letter within a column are not            significantly different (P > 0.05; Duncan's [1951] multiple range test);      0.02 ml dosage; 6 replicates.                                                 .sup.c High A.sub.1 /A.sub.2 consists of isomers A.sub.1, A.sub.2, B.sub.     and B.sub.2 wherein isomers A.sub.1 and A.sub.2 are more than 50% of the      blend. High B.sub.1 /B.sub.2 consists of isomers A.sub.1, A.sub.2, B.sub.     and B.sub.2 wherein isomers B.sub.1 and B.sub.2 are more than 50% of the      blend.                                                                        .sup.d Contained ca. 2.5% isomer B1.                                     

We claim:
 1. A composition to attract the Mediterranean Fruit Flyhaving, as an attractant, comprising an effective amount of a compoundof the formula ##STR3## wherein --CH₃ and --COOR are in thetrans-configuration and the iodo atom is equatorial, and wherein R isselected from the group consisting of ethyl, 2,2,2-trifluoroethyl,propyl, 1-methylethyl, and 1-methyl-2,2,2-trifluoroethyl, wherein saidcomposition essentially is free of isomers of said compound having theiodo atom in the axial position.
 2. The composition of claim 1 furtherincluding an inert carrier for said compound.
 3. The composition ofclaim 1 further including a control agent for the Mediterranean FruitFly.
 4. An composition to attract the Mediterranean Fruit Fly having, asan attractant, an effective amount of a mixture of compounds of theformulas ##STR4## wherein --CH₃ and --COOR are in thetrans-configuration and the iodo atom is equatorial, and wherein R isselected from the group consisting of ethyl, 2,2,2-trifluoroethyl,propyl, 1-methylethyl, and 1-methyl-2,2,2-trifluoroethyl, wherein saidcomposition essentially is free of isomers of said compounds having theiodo atom in the axial position, said R in each of the formulas beingidentical.
 5. The composition of claim 4 further including an inertcarrier for said compounds.
 6. The composition of claim 4 furtherincluding a control agent for the Mediterranean Fruit Fly.
 7. Acomposition to attract the Mediterranean Fruit Fly having, as anattractant, an effective amount of a mixture of compounds of theformulas ##STR5## wherein --CH₃ and --COOR are in thetrans-configuration and the iodo atom is equatorial and axial, but ismore than 50% equatorial, and wherein R is selected from the groupconsisting of ethyl 2,2,2-trifluoroethyl, propyl, 1-methylethyl, and1-methyl-2,2,2-trifluoroethyl, said R in each of the formulas beingidentical.
 8. The composition of claim 7 wherein R is ethyl.
 9. Thecomposition of claim 7 wherein R is propyl.
 10. The composition of claim7 wherein R is 2,2,2-trifluoroethyl.
 11. The composition of claim 7further including an inert carrier for said compounds.
 12. Thecomposition of claim 7 further including a control agent for theMediterranean Fruit Fly.
 13. The composition of claim 12 where saidcontrol agent is an insecticide.
 14. A method of attracting theMediterranean Fruit Fly comprising subjecting said Fly for an extendedperiod of time to a composition having, as an attractant, an effectiveamount of a compound of the formula ##STR6## wherein --CH₃ and --COORare in the trans-configuration and the iodo atom is equatorial, andwherein R is selected from the group consisting of ethyl,2,2,2-trifluoroethyl, propyl, 1-methylethyl, and1-methyl-2,2,2-trifluoroethyl, wherein said composition essentially isfree of isomers of said compound having the iodo atom in the axialposition.
 15. A method of attracting the Mediterranean Fruit Flycomprising subjecting said Fly for an extended period of time to acomposition having, as an attractant, an effective amount of a mixtureof compounds of the formulas ##STR7## wherein --CH₃ and --COOR are inthe trans-configuration and the iodo atom is equatorial, and wherein Ris selected from the group consisting of ethyl, 2,2,2-trifluoroethyl,propyl, 1-methylethyl, and 1-methyl-2,2,2-trifluoroethyl, wherein saidcomposition essentially is free of isomers of said compounds having theiodo atom in the axial position, said R in each of the formulas beingidentical.
 16. A method of attracting the Mediterranean Fruit Flycomprising subjecting said Fly for an extended period of time to acomposition having, as an attractant, an effective amount of a mixtureof compounds of the formulas ##STR8## wherein --CH₃ and --COOR are inthe trans-configuration and the iodo atom is equatorial and axial, butis more than 50% equatorial, and wherein R is selected from the groupconsisting of ethyl, 2,2,2-trifluoroethyl, propyl, 1-methylethyl, and1-methyl-2,2,2-trifluoroethyl, said R in each of the formulas beingidentical.
 17. The method of claim 16 wherein R is ethyl.
 18. The methodof claim 16 wherein R is propyl.
 19. The method of claim 16 wherein R is2,2,2-trifluoroethyl.
 20. The method of claim 17 further including aninert carrier for said compounds.
 21. The method of claim 17 furtherincluding a control agent for the Mediterranean Fruit Fly.
 22. Themethod of claim 21 wherein said control agent is an insecticide.